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THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. 900 THIRD AVENUE I NEW YORK. N.Y. 10022 Memorandum To: Dr. H.McAllister and Staff Fran: D.H.Ford Re: Site visit with Dr. R. Costa, University of Illinois at Chicago, I1.,Nov. 3, 1993 Grant No. 2822A entitled "Analysis of the HNF-3/fkh DNA-binding proteins in cell-specific transcription." Dr. Costa's laboratory is concerned with an analysis of the liver transcription factors HNF-3a and-3(3 , which are critical for hepatocyte differentiation.CTR support has inabled him to develop a PCR protocol which led to the amplification of HNF-3/fkh homologue (HFH) clones from various mammalian tissues cDNAs. His new goals are directed toward elucidating the role of the HNF-3/fkh family in tissue-specific gene regulation. Aims: Analize HFH adult and embryonic cellular expression patterns. Identify HFH DNA binding sites and determine if HFH proteins are transcriptional activators or repressors. Progress: Dr. Costa's progress durint,) his first 3-year:support from CTR is amply described in his progress report which accompanied his compettive renewal (approved in Sept. 1993) and thus need not be further discussed. During this period of support, two publications which ACK CTR appeared: "Hepatocyte nuclear factor 3 contains two transcriptional activation domains, one of whi:ch is conserved with the Drosophila fork head protein."Pani, et al. Mol.Cell Biol. 12:3733, 1992; and "Identification of nine tissue-specific transcription facots of the hepatocyte nucL.ear factor 3/forkhead DNA-binding domain family."Proc. Nat. Acad.Sci. 90:3948,1993. Inasmuch as Dr. Eisenberg visited Dr. Costa only a short while ago, my visit was more in the nature of a courtesy visit following a visit with Dr. Bagchi just down the street from his lab. Comment: Dr. Costa is a young, enthusiastic investigator excited by how genes regulate expression and how the results of their expression is then active in regulation of transcription. It also appears from our discussion that while he is focussing on the expression of 5 HFH cDNAs in lung, brain and kidney, similar investigations~could be made with other organs in relation to differentiation. Further, since these factors may act as either promotors or suppre sors, will they function.as a promotor in one organ and a suessor in an other and/or are there other factors which will influence the type of activity expressed, or could they be promotors in embryos and suppressor in adults? Thus, one can see that Dr. Costa has a lot of interesting aspects of his program to consider, all of which are probably important in cellular and organ differ.er,tiation and function. DHF